Replication-defective vector based on a chimpanzee adenovirus

An adenovirus previously isolated from a mesenteric lymph node from a chimp anzee was fully sequenced and found to be similar in overall structure to h uman adenoviruses. The genome of this virus, called C68, is 36,521 bp in le ngth and is most similar to subgroup E of human adenovirus, with 90% identi ty in most adenovirus type 4 open reading frames that have been sequenced. Substantial differences in the hexon hypervariable regions were noted betwe en C68 and other known adenoviruses, including adenovirus type 4. Neutraliz ing antibodies to C68 were highly prevalent in sera from a population of ch impanzees, while sera from humans and rhesus monkeys failed to neutralize C 68. Furthermore, infection with C68 was not neutralized from sera of mice i mmunized with human adenovirus serotypes 2, 4, 5, 7, and 12. A replication- defective version of C68 was created by replacing the E1a and E1b genes wit h a minigene cassette; this vector was efficiently transcomplemented by the E1 region of human adenovirus type 5. C68 vector transduced a number of hu man and murine cell lines. This nonhuman adenoviral vector is sufficiently similar to human serotypes to allow growth in 293 cells and transduction of cells expressing the coxsackievirus and adenovirus receptor. As it is diss imilar in regions such as the hexon hypervariable domains, C68 vector avoid s significant cross-neutralization by sera directed against human serotypes .